Radiobiological and Molecular Biological Study of Enhancement Effect of High LET Heavy Ion Irradiation and Chemotherapeutic Agents in vitro

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We investigate the differences between two rat yolk sac tumor cell lines with different radiosensitivities in sensitivity to high-LET heavy ion beam and in sensitizing effect and the mechanism of cisplatin and etoposide in combination with heavy-ion beam. NMT-1 (wild-type p53 cell) is a parent radiosensitive cell line and NMT-1R (mutant-type p53 cell) is a variant radioresistant cell line. The dose average LET value in the samples was 80 keV/μm. The concentration of chemotherapeutic agents required to reduce colony formation by 50% at 1-hour treatment (IC50 of etoposide) was selected for heavy ion irradiation pretreatment for each cell line. The mechanism of the enhancement effect was investigated by apoptosis and cell cycle and mechanism of DNA repair. The RBE of carbon beam was larger in mutant-type p53 cells than in wild-type p53 cells. Etoposide showed a synergistic effect in combination with carbon beam irradiation in NMT-1R cells. However, there was no enhancement effect in radiosensitive NMT-1 cells. The incidence of apoptosis, the distribution of cell cycle and the ability of DNA repair did not change between carbon beam irradiation alone and the combination of carbon beam irradiation and etoposide od cisplation in both cell lines.